2012
DOI: 10.1038/bjc.2012.563
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Melatonin induces transcriptional regulation of Bim by FoxO3a in HepG2 cells

Abstract: Background:Melatonin induces apoptosis in many different cancer cell lines, including hepatocellular carcinoma cells. However, the responsible pathways have not been clearly elucidated. A member of the forkhead transcription factors' family, FoxO3a, has been implicated in the expression of the proapoptotic protein Bim (a Bcl-2-interacting mediator of cell death). In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate whether melatonin treatment induces Bim through regulation … Show more

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Cited by 70 publications
(75 citation statements)
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“…In kidney tumors, melatonin enhances the apoptotic effect of endoplasmic reticulum stress-inducer, thapsigargin. As previously reported for hepatocarcinoma cells [97], this effect is mediated by a melatonin-related increase in CHOP expression [116].…”
Section: Melatonin and Other Cancerssupporting
confidence: 74%
See 1 more Smart Citation
“…In kidney tumors, melatonin enhances the apoptotic effect of endoplasmic reticulum stress-inducer, thapsigargin. As previously reported for hepatocarcinoma cells [97], this effect is mediated by a melatonin-related increase in CHOP expression [116].…”
Section: Melatonin and Other Cancerssupporting
confidence: 74%
“…It is likely that melatonin effects in liver cancer are mediated by different and interacting pathways, including upregulation of FoxO3a-mediated activation of pro-apoptotic protein Bim [97], and enhanced endoplasmic reticulum stress-induced apoptosis through inhibition of COX-2 expression and reduction of Bcl-2 levels, and by an elevation of the pro-apoptotic transcription factor CHOP [98]. Melatonin has also been shown to synergistically promote chemotherapy-induced apoptosis in hepatoma cells, mainly through the downregulation of Bcl-2 and the elevation of pro-apoptotic proteins [99].…”
Section: Melatonin In Gastrointestinal and Colon Cancersmentioning
confidence: 99%
“…For example, paclitaxel can induce Bim EL expression and subsequently cell apoptosis via increasing FoxO3a expression in MCF-7 breast cancer cells (48). Similarly, melatonin can induce apoptosis in HepG2 hepatocarcinoma cells through the upregulation of Bim mediated by nuclear translocation and activation of the transcription factor FoxO3a (49). In the present study, imidazole upregulated the protein level of Foxo3a and induced its increased nuclear localisation, suggesting a possible association between FoxO3a as a transcription factor of Bim in HEC-1B cells.…”
Section: Discussionmentioning
confidence: 99%
“…Nowadays melatonin, the main product of the pineal gland, has attracted increasing attention because of its protective role in several pathophysiological situations, including different cancer types, where it exerts oncostatic effects (Hill and Blask, 1988; Farriol et al , 2000; Futagami et al , 2001; Cini et al , 2005; Garcia-Santos et al , 2006; Garcia-Navarro et al , 2007; Mauriz et al , 2007; Cabrera et al , 2010; Chiu et al , 2010; Gonzalez et al , 2010; Carbajo-Pescador et al , 2011, 2013). Our group has shown the melatonin oncostatic activity in HepG2 liver tumour cells, highlighting its pro-apoptotic properties through upregulation of cell death-related processes (Martin-Renedo et al , 2008; Carbajo-Pescador et al , 2009, 2011, 2013).…”
mentioning
confidence: 99%